CN101001613B - Porous article as liquid agent carrier - Google Patents

Abstract

A novel tablet product that in an easy, flexible and reproducible manner can be loaded with a relatively high amount of a pharmaceutically acceptable liquid formulation e.g. carrying a therapeutically, prophylactically and/or diagnostically active substance. The novel loadable tablet product may be produced in large-scale batches and stored until use and each batch or sub-batch may be loaded with the same or different pharmaceutically acceptable liquid formulations and/or active substances. A loadable tablet according to the invention has a porosity of 30% v/v or more. The invention also provides tablets that have been loaded with such a liquid formulation as well as a method for the preparation thereof.

Description

It is used as the porous tablet of liquid preparation carrier

Invention field

The present invention relates to the novel tablet product for the pharmaceutically acceptable liquid preparation that relatively high amount can be loaded with facility, flexible and reproducible mode, for example, described liquid preparation carries treatment, prevention and/or diagnosis active material.With this novel tablet product of large-scale mass production and it can store untill use, and each batch or sub-batch can be loaded with identical or different pharmaceutically acceptable liquid preparation and/or active material.Present invention also offers tablet for being loaded with this kind of liquid preparation and preparation method thereof.

The invention provides the method for obtaining tablet, the tablet is comprising the influence of the active material and appropriate relatively high amount active material accessibility so as to the liquid for for example discharging and/or absorbing when being administered orally.

Background of invention

Many drug substances have unwanted characteristic, and it is expected that many in the drug substance in future also has unwanted characteristic, especially in terms of such as water-soluble and oral administration biaavailability.Hence it is highly desirable to so that easily prophylactic activity material is delivered to body while treatment and/or prophylactic response needed for can producing by mode relatively.

In pharmaceutical field, the pharmaceutical composition comprising one or more active materials and various excipient is generally prepared.A reason for preparing this kind of pharmaceutical composition is that the utilization rate of reactive compound can be operated after intake described pharmaceutical composition.

In order to prepare the pharmaceutical composition of oral administration, active material is generally mixed to the preparation of aggregation, can be with reactive compound tabletted or in the form of being packed into capsule to provide.

Except provide can be with the active material of tabletted form in addition to, aggregation can also be designed so as to obtain (secure) intake containing the particle pharmaceutical composition after reactive compound required utilization rate.

Improve that to be insoluble in the oral administration biaavailability of the medicine of water and provide the quite water miscible medicines that has of sustained release forms be still one of most challenging aspect in medicament research and development, and the further research and development of aggregation technique can be that provide valuable instrument in terms of these.

A kind of common technology for granulation is wet granulation, wherein by mixture of powders and liquid including reactive compound, usually liquid, aqueous mixing under the mechanical pressure for preparing particle.Particle generally prepared by wet granulation using preceding.

Fusing aggregation and controlled aggregation are the aggregation technique for reactive compound, and the reactive compound carried out especially by the following steps is assembled：Pharmaceutically acceptable carrier is melted, such as oil or oil sample material；One or more reactive compounds are dissolved or dispersed in the carrier of fusing and the mixture thus prepared is deposited on particulate matter, i.e. filler, and then particle is adhered each other and forms aggregation.

The new technology of controlled aggregation is described in WO 03/004001 (present inventor), the oil or oil sample material of relatively high amount can be loaded to particulate matter by this technology.The technology is based on the method including being sprayed on the carrier compositions containing oil or oil sample material on particulate matter.The condition of this method can load the oil or oil sample material of relatively high amount to particulate matter.This method generally includes heating carrier composition and the temperature of the carrier compositions is maintained in application process.It is used as the application implemented by spraying, it is desirable to the problem of temperature of strict control spraying apparatus is to avoid related to nozzle grumeleuse etc..

Description of the invention

Present inventor has had now been found that simpler solution.They find to prepare only containing be subjected on inert medicine excipient tablet (but, in some cases, wherein it is also suitable for mixing active material), and when the tablet contacts the pharmaceutically acceptable liquid preparation for example containing active material, liquid preparation can be sucked tablet by this tablet because of its porosity.Most surprisingly, it can be loaded and reproduce in this inert tablet within the relative short time time limit, i.e. when the tablet and liquid preparation using same type and size, it may be inhaled same amount of liquid preparation (referring to the embodiments herein).For the best knowledge that present inventor can know about, before this in liquid, such as pharmaceutical field of the liquid containing active material are loaded to tablet, not yet recognize and using the inert tablet with above-mentioned characteristic.

The formulation comprising porous particle is described in WO 00/38655 (Alza Corporation).The formulation can be the tablet form that such as prepared by mixed with propylene glycol by by porous particle and liquid-carrier.However, with the present invention on the contrary, there is no description in the documents with absorbing the ability of liquid active substance or lipophilic medium containing one or more active materials in reproducible mode and produce the inert tablet of high liquid loading capacity.

EP-A-0 001 247 is related to the preparation that the nifedipine of oral administration carries the nifedipine of the noncrystalline dispersion form of solution or nifedipine in polyvinylpyrrolidone in polyethylene glycol on pharmaceutically acceptable porous carrier.The inert tablet for being suitable to carrying is not described.

US 6,399,591 (Yung-Shin Pharmaceutical Ind.Co.Ltd.), which is related to, includes the blank tablet of absorbent, disintegrant, lubricant and diluent or adhesive, or the mixture of diluent and adhesive.The active component of liquid form is introduced blank tablet to produce pharmaceutical composition.However, embodiment represents only obtain about 13%w/w loading capacity.

The tablet that can be provided to the present invention loads any type of active material, as long as can be designed to them can carry out any type of active material release.

The loading capacity of inert tablet depends on the type and property for including pharmaceutically acceptable excipient in tablets.However, key parameter is not only in that the characteristic of the pharmaceutically acceptable excipient included in tablet, and it is the characteristic of tablet itself.For the purpose of it, the characteristic of most critical is following tablet ability：I) enough pharmaceutically acceptable liquid preparations are absorbed；Ii the uptake) is maintained to be evaporated without having the amount of any liquid preparation from tablet surface in storage process；And iii) once making tablet carry out In Vitro Dissolution experiment and/or to subject, such as animal includes oral administration in human, just release active material.

In order to meet these requirements, inventors have determined that the key characteristic of the tablet of loading is the porosity of the tablet.Therefore, the present invention is related to the tablet for being suitable to carrying with 30%v/v or more than 30%v/v porositys in an aspect, and it is used as the drug carrier composition of pharmaceutically acceptable liquid preparation.The conventional tablet used in pharmaceutical field has much lower porosity.Avoid using be one of the reason for unusual porous tablet this kind of tablet without can in packaging and storage process normal operating tablet sufficiently solid property, i.e., it is estimated they the requirement of pharmacopeia can not be met in terms of hardness and friability.

According to the equation 1 in embodiment hereof, porosity is defined as the space in tablet and the volume ratio of tablet cumulative volume.

Tablet suitable for carrying

Term " inert tablet " in the context of the present invention be used for represent only containing be typically considered in terms of therapeutic action be inert component tablet.More specifically, this kind of tablet contains pharmaceutically acceptable excipient, and they are selected from the group of the compositions such as filler, diluent, adhesive, lubricant, glidant.Additive is all if any such as pH adjusting agent, buffer, accelerator, wetting agent, solubilizer, surfactant, antioxidant.The term " tablet for being suitable to carrying " used in the context of the invention is represented " inert tablet " as described above, and further has at least about 30%v/v porosity, so as to suitably load liquid.However, in some cases, focusing on this kind of tablet includes active material, and thus term " tablet for being suitable to carrying " also includes this kind of situation.In preferred embodiments, tablet is " inert and suitable for carrying ", that is, without any active material inclusion before loading.

But, just as illustrated in the examples herein, inventors have discovered that the tablet with high porosity can be given to load pharmaceutically acceptable liquid, the liquid preferably comprises one or more treatments, prevention and/or diagnosis active material (being hereinbelow abbreviated as " active material ").The tablet of loading there is enough robustnesses (such as being coated), packaging, storage be processed further to be resistant to during normal tablets operation, i.e., they meet the requirement of pharmacopeia in terms of hardness and friability.

In a specific embodiment, the present invention is suitable to the tablet of carrying in test as described herein, so that tablet can load at least 20%w/w such as, for example, at least 25%w/w or at least 30%w/w corn oil (gross weight of solid dosage forms during based on loading).This kind of experiment can ensure that tablet has the ability for absorbing and being applied to liquid preparation prepared by tablet.

As described above, the tablet that the present invention is suitable to carrying has enough robustnesses to be resistant to normal tableting operation, i.e. they have 20N or more than 20N hardness, such as, e.g., from about 25N or more than 25N hardness, about 30N or more than 30N hardness, about 35N or more than 35N hardness, the hardness of about 40N or more than 40N hardness, about 45N or more than 45N, or about 50N or more than 50N hardness.

In addition, the tablet of the present invention has about 5% or less than 5%, such as, e.g., from about 4% or less than 4%, about 3% or less than 3%, about 2% or less than 2%, such as about 1% or less than 1% friability.

As described above, the tablet that the present invention is suitable to carrying includes one or more pharmaceutically acceptable excipient.It is important, however, that at least one pharmaceutically acceptable excipient has correct characteristic in terms of the tablet of 30%v/v or more than 30%v/v porositys is provided, and the amount of the excipient is enough to make the tablet of acquisition also to have required porosity.In some cases, this kind of pharmaceutically acceptable excipient is described as " excipient for providing pharmaceutically acceptable porosity ".For this purpose, inventors have discovered that, if by pharmaceutically acceptable excipient and acceptable excipient on the at most 50%w/w lactose or other medicines for direct pressing, such as, the tablet that such as Emcompress is made tablet and obtained together has 30vol% or more than 30vol% porosity, then this pharmaceutically acceptable excipient is applicable in the context of the present invention.The quality of lactose reaches the standard for direct pressing.

In the tablet suitable for carrying, the summation of pharmaceutically acceptable excipient with above-mentioned characteristic (meeting above-mentioned experiment) is equivalent at least 50%w/w, such as, for example, at least 55%w/w, at least 60%w/w, at least 65%w/w, at least 70%w/w, at least 80%w/w, at least 90%w/w, at least 95%w/w or at least 98%w/w, such as, such as 100%w/w tablet total weight.

In preferred in terms of, it is about 50%w/w or more than 50%w/w to provide the presence concentration of the excipient of one or more porositys in tablets, such as, e.g., from about 60%w/w or more than 60%w/w, such as, e.g., from about 70%w/w or more than 70%w/w, about 80%w/w or more than 80%w/w, about 90%w/w or more than 90%w/w, or about 95%w/w or more than 95%w/w.

In addition, the specific surface area (BET surface area) that concern provides the excipient of porosity should be relatively large, such as, for example, be determined by gas absorption and be at least 50m²/g。

The pharmaceutically acceptable excipient example list with the appropriate characteristics that can provide the tablet that the present invention is suitable to carrying has been given below.Each pharmaceutically acceptable excipient can be used alone or be combined, as long as having reached all purposes in terms of porosity.

For the purpose of it, it should be noted that by using certain press power by tablet press piece agent.However, press power can be not necessarily very low, so that the requirement in terms of tablet hardness and friability is mutually traded off, i.e., these requirements ensure that tablet has enough robustnesses.

Can be used for obtaining tablet of the present invention with 30%v/v or more than 30%v/v porositys suitable pharmaceutically acceptable excipient be selected from metal oxide, metal silicate, metal carbonate, metal phosphate, metal sulfate, glycitols, carbohydrate and cellulose and cellulose derivative group into group.Metal is selected generally from the group of sodium, potassium, magnesium, calcium, zinc, aluminium, titanium and silicon composition.

Suitable metal oxide for the present invention is selected from the group of following material composition：Magnesia；Calcium oxide；Zinc oxide；Aluminum oxide；Titanium dioxide, including Tronox A-HP-328 and TronoxA-HP-100；Silica, including Aerosil, Cab-O-Sil, Syloid, Aeroperl, Sunsil (silica bead), Zeofree, Sipernat；And its mixture.

In a specific embodiment, metal oxide is titanium dioxide or silica or its mixture.

Silicate can be divided into the following group：

● the swellable clay of smectite class, such as bentonite, aluminium-magnesium silicate, laponite.

● aluminium hydrosilicate or alkaline-earth metal.Neusilin belongs to the group and the polymerization (Neusilin US2) based on synthesis.

● silica is separated into porous and non-porous silica：

Zero non-porous colloidal silica, such as Aerosil (pyrogenic silica)；

Zero Bio-sil, such as Syloid, Porasil, Lichrosorp；

Zero is other, such as Zeopharm S170, Zeopharm 6000, Aeroperl 300；

Therefore, the present invention be suitable to carrying tablet can contain for non-porous silicate including Aerosil types pyrogenic silica and/or porous silicate including, such as Syloid, Porasil and Lichrosorp metal oxide.

In other embodiments, the pharmaceutically acceptable excipient for the present invention is metal silicate, and they are selected from the group of following material composition：Sodium metasilicate；Potassium silicate；Magnesium silicate；Calcium silicates, including synthetic calcium silicate, such as, such as Hubersorp；Zinc silicate；Alumina silicate；Sodium silicoaluminate, such as, such as Zeolex；Magnesiumaluminumsilicate (magnesium aluminum silicate)；Magnesium aluminometasilicate (magnesium aluminum metasilicate)；Metasilicic acid aluminium (aluminiummetasilicate)；Neusilin SG2；Neusilin US2；And its mixture.

Metal silicate can also be selected from bentonite, aluminium-magnesium silicate and synthesis of clay constitute group smectite class swellable clay, and/or the magnesium aluminometasilicate selected from alkaline-earth-metal silicate and including alumina silicate metal silicate.In a specific embodiment, described metal silicate is Neusilin.

As described above, suitable pharmaceutically acceptable excipient can be metal carbonate, the carbonate of the group such as constituted selected from sodium carbonate, sodium acid carbonate, potassium carbonate, saleratus, calcium carbonate, magnesium carbonate, zinc carbonate and aluminium carbonate and its mixture.

Other metal salts suitable for the present invention are metal phosphate, and they are selected from the group of sodium phosphate, disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, calcium phosphate, magnesium phosphate, trbasic zinc phosphate and aluminum phosphate composition.

More specifically, pharmaceutically acceptable excipient can be the calcium phosphate of the group constituted selected from anhydrous Bibasic Calcium Phosphate, Bibasic Calcium Phosphate dihydrate and tricalcium phosphate.

Anhydrous Bibasic Calcium Phosphate is selected generally from the group of A-Tab, calcium monohydrogenphosphate, tricalcium orthophosphate, Di-Cafos AN, orthophosphoric acid dicalcium, E341, anhydrous Emcompress, Fujicalin, synthos (1: 1) and secondary calcium phosphate and its mixture composition.Bibasic Calcium Phosphate dihydrate can be selected from Cafos, Cafos, E341, Calipharm, Calstar, Di-Cafos, orthophosphoric acid dicalcium, Di-TAB, Emcompress, synthos (1: 1) dihydrate, secondary calcium phosphate, the group of Fujiclin SG compositions.

The example of tricalcium phosphate is, for example, hydroxyapatite, synthos (2: 3), precipitated calcium phosphate, tertiary calcium phosphate, Tri-Cafos, two orthophosphate tricalciques, orthophosphate tricalcique, tricalcium phosphate, TRI-CAL, WG, TRI-TAB.

Other suitable metal salts are metal sulfate, such as, such as sodium sulphate, niter cake, potassium sulfate, potassium acid sulfate, calcium sulfate, magnesium sulfate, zinc sulfate and/or aluminum sulfate.

The example of suitable sulfate is, for example,：Dead plaster, including dental stone, anhydrous gypsum, the anhydrous sulfate of lime, Destab, Drierte, E516, anhydrite, anhydrite and Snow White, or calcium sulfate dihydrate, including alabaster, Cal-Tab, Compactrol, Destab, E516, gypsum, light spar, ore deposit are white, puritan filler calcium, sulfate precipitate calcium, dabllite, cebollite, selenite, land plaster and USG land plasters.

In other embodiments, pharmaceutically acceptable excipient can be selected from sorbierite (such as, such as Sorbogem, SPI Pharma), xylitol, mannitol (such as, such as Mannogem, SPI Pharma), maltitol, inositol, mannitol (such as Pealitol SP 100) composition group sugar alcohol and/or it can be the group selected from following material composition sugar：Single-, two- or polysaccharide, including sucrose, glucose, fructose, sorbose, xylose, lactose, glucan, glucan derivative, cyclodextrin.

Cellulose and cellulose derivative are also the suitable pharmaceutically acceptable excipient for obtaining the tablet purpose with 30%v/v or more than 30%v/v porositys.Example includes：Cellulose；Microcrystalline cellulose；Celphere；Cellulose derivative, including porous cellulose pearl：Cellulose acetate Celluflow TA-25 and cellulose Celluflow C-25, hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC), methylcellulose, ethyl cellulose, sodium carboxymethylcellulose, hydroxyethyl cellulose etc..

It is suitable to acceptable excipient on the other medicines of the tablet of carrying for the present invention

Tablet suitable for carrying can also contain acceptable excipient, such as those excipient for being usually used in preparing tablet on other medicines certainly.

In the context of the present invention, the pharmaceutically acceptable excipient of term " " is to be expressed as inert arbitrary substance, and it is meant that itself does not have any treatment and/or prevention effect substantially.The purpose that this kind of excipient can be added is to result in medicine, cosmetics and/or food compositions with acceptable technical characteristic.

Being suitable to the suitable excipient example of the tablet of carrying for the present invention includes filler, diluent, disintegrant, adhesive, lubricant etc. or its mixture.When the composition or crystalline solid form of the present invention can be used for different purposes, this kind of different application selection excipient generally may be considered as.It is, for example, acidulant, basifier, preservative, antioxidant, buffer, chelating agent, colouring agent, compound system, emulsifying agent and/or solubilizer, flavouring and spices, NMF, sweetener, wetting agent etc. to be suitable for acceptable excipient on the other medicines of application.

The example of suitable filler, diluent and/or adhesive includes：Lactose (lactose, alpha-lactose, beta lactose, the Tabletose of such as spray drying

, various grades Pharmatose、MicrotoseOr Fast-Floc

)；Microcrystalline cellulose (the Avicel of various grades

、Elcema

、Vivacel

、Ming Tai

Or Solka-Floc

)；Hydroxypropyl cellulose, L- hydroxypropyl celluloses (low substituted), hydroxypropyl methyl cellulose (HPMC) (such as Methocel E, F and K, Shin-Etsu, Ltd Metolose SH, such as, the SH of Methocel E and Metolose 60 of such as 4,000cps grades；The SH of Methocel F and Metolose 65 of 4,000cps grades；4,000th, the Methocel K of 15,000 and 100,000cps grades；With 4,000th, 15,000th, 39,000 and 100, the SH of Metolose 90 of 000 grade), methyl cellulose polymers (such as, such as Methocel A, Methocel A4C, Methocel A15C, Methocel A4M), hydroxyethyl cellulose, sodium carboxymethylcellulose, carboxylic methylene (carboxymethyene), carboxymethyl hydroxyethyl cellulose and other cellulose derivatives；Sucrose, agarose, sorbierite, mannitol, dextrin, maltodextrin, starch or modified starch (including farina, cornstarch and rice starch)；Calcium phosphate (such as basic calcium phosphate, calcium monohydrogen phosphate, Dicalcium Phosphate hydrate)；Calcium sulfate；Calcium carbonate；Mosanom；Collagen etc..

The instantiation of diluent is, for example, calcium carbonate, Bibasic Calcium Phosphate, tricalcium phosphate, calcium sulfate, microcrystalline cellulose, powdered cellulose, glucan, dextrin, glucose, fructose, kaolin, lactose, mannitol, sorbierite, starch, pregelatinized starch, sucrose, sugar etc..

The instantiation of disintegrant is, for example, alginic acid or alginates, microcrystalline cellulose, hydroxypropyl cellulose and other cellulose derivatives, cross-linked carboxymethyl cellulose sodium, Crospovidone, polacrilin potassium (polacrillin potassium), sodium starch glycollate, starch, pregelatinized starch, CMS (such as PrimogelAnd Explotab

) etc..

The instantiation of adhesive is, for example, Arabic gum, alginic acid, agar, calcium carrageenan, sodium carboxymethylcellulose, microcrystalline cellulose, dextrin, ethyl cellulose, gelatin, liquid glucose, guar gum, hydroxypropyl methyl cellulose, methylcellulose, pectin, PEG, PVP, pregelatinized starch etc..

Glidant and lubricant can also be included in tablet.Example includes stearic acid, magnesium stearate, calcium stearate or other metallic stearates, talcum powder, wax and glyceride type, light mineral oil, PEG, glyceryl behenate, colloidal silica, hydrogenated vegetable oil, cornstarch, sodium stearyl fumarate, polyethylene glycols, alkyl sulfate, sodium benzoate, sodium acetate etc..

It is, for example, flavouring, colouring agent, taste masked agent, pH- conditioning agents, buffer, preservative, stabilizer, antioxidant, wetting agent, moisture regulator, surfactant, suspending agent, sorbefacient, improvement release reagent etc. that the present invention, which can be included in, suitable for other excipient in the tablet of carrying.

Other additives in the present composition or solid dosage forms can be antioxidant, such as ascorbic acid, ascorbyl palmitate, Butylated Hydroxyanisole, Butylated Hydroxytoluene, hypophosphorous acid, monothioglycerol, potassium metabisulfite, propyl gallate, sodium formaldehyde sulphoxylate, sodium pyrosulfite, sodium thiosulfate, sulfur dioxide, tocopherol, alpha-tocopherol acetate, hemisuccinic acid vitamin E, TPGS or other Tocopheryl derivatives.Carrier compositions can also contain：Such as stabilizer.The general about 0.1%w/w- of the concentration of antioxidant and/or stabilizer in carrier compositions about 5%w/w.

The composition or solid dosage forms of the present invention can also include one or more surfactants or the material with surfactant properties.Notice this kind of such material being related in microsolubility active material moistening and thus promote the dissolubility of active material to make moderate progress.

The example about surfactant has been given below.

It is this kind of surfactant for the suitable surfactant in Tablets, such as, such as entitled Lipocine, those amphiphilic surfactants disclosed in Inc. WO 00/50007.It is about the example of surfactant：

I) Polyethoxylated fatty acids, such as, the esters of aliphatic acid one-or two of such as polyethylene glycol or its mixture, such as, such as polyethylene glycol and laurate, oleic acid, stearic acid, myristic acid, one-or two esters of castor oil acid, and polyethylene glycol can be selected from PEG4, PEG5, PEG6, PEG7, PEG8, PEG9, PEG10, PEG12, PEG15, PEG20, PEG25, PEG30, PEG32, PEG40, PEG45, PEG50, PEG55, PEG100, PEG200, PEG400, PEG600, PEG800, PEG1000, PEG2000, PEG3000, PEG4000, PEG5000, PEG6000, PEG7000, PEG8000, PEG9000, PEG1000, PEG10, 000, PEG15, 000, PEG20, 000, PEG35, 000；

Ii) polyethylene glycol glycerol fatty acid ester, i.e., esters described above, but be the glyceride type form of each aliphatic acid；

Iii) with glycerine, propane diols, ethylene glycol, PEG or the sorbierite esters of such as vegetable oil, described vegetable oil is such as：Such as rilanit special, apricot kernel oil, palm-kernel oil, castor oil, apricot kernel oil, olive oil, peanut oil, hydrogenated palm kernel oil；

Iv) Polyglycerized fatty acids, such as：Such as polyglycerol stearate.Unigly GO 102S, polyglycereol ricinoleate ester, polyglyceryl linoleate；

V) methyl glycol fatty acid ester class, such as, such as PGML, propylene glycol ricinoleate；

Vi) single-and two glyceride types, such as：Such as glyceryl monooleate, glyceryl dioleate, list-and/or glyceryl dioleate, glycerol caprylate, glycerol decanoate；

Vii) sterol and steroid derivatives；

Viii) polyethylene glycol sorbitan fatty acid esters class (PEG- sorbitan fatty acid esters class), PEG esters and various Tween such as with above-mentioned different molecular weight

Series；

Ix) polyethylene glycol alkyl ether class, such as, such as PEG oil ethers and PEG lauryl ethers；

X) sugar esters, such as：Such as sucrose palmitic acid ester and sucrose monolaurate；

Xi) Polyethylene glycol alkyl phenols class, such as：Such as Triton

X or N series；

Xii) polyox-yethylene-polyoxypropylene block copolymer, such as, such as Pluronic

Series, Synperonic

Series, Emkalyx

、Lutrol

、Supronic

Deng.These polymer are collectively referred to as " poloxamer class ", and the related example in the context of the invention is poloxamer 105,108,122,123,124,181,182,183,184,185,188,212,215,217,231,234,235,237,238,282,284,288,331,333,334,335,338,401,402,403 and 407；

Xiii) sorbitan fatty acid esters class, such as Span

Series or Ariacel

Series, such as, such as sorbitan palm monolaurate, span 40, dehydrated sorbitol mono-fatty acid ester, sorbitan monostearate；

Xiv) lower alcohol fatty acid esters class, such as：Such as oleate, isopropyl myristate, isopropyl palmitate；

Xv) ionic surface active agent, including cationic, anionic and zwitterionic surfactant, such as, such as soap, bile salt, phospholipid, phosphate, carboxylic acid esters, sulfuric acid ester and sulfonic acid esters.

When surfactant or surfactant mixture are present in the present composition or solid dosage forms, the concentration of surfactant is general in about 0.1-80%w/w, such as, e.g., from about 0.1- about 20%w/w, about 0.1- about 15%w/w, about 0.5- about 10%w/w or scope, or in about 0.10- about 80%w/w, such as, e.g., from about 10- about 70%w/w, about 20- about 60%w/w or about 30- about 50%w/w scope.

It is loaded with the tablet of pharmaceutically acceptable liquid

Design above-mentioned tablet, so as to load pharmaceutically acceptable liquid preparation to them, concentration is about 20%w/w or more than 20%w/w, such as, e.g., from about 25%w/w or more than 25%w/w, about 30%w/w or more than 30%w/w (gross weight of solid dosage forms during based on loading).Therefore, in another aspect of the present invention, it is related to this kind of tablet.

In preferred in terms of, the presence concentration of pharmaceutically acceptable liquid preparation is about 40%w/w or more than 40%w/w, such as, e.g., from about 50%w/w or more than 50%w/w, or about 60%w/w or more than 60%w/w (gross weight of solid dosage forms during based on loading).

The key parameter related to liquid preparation loading is the viscosity of liquid preparation.Can be in any way possible, such as, for example by placing a tablet into the suitable vessel containing liquid or by being loaded liquid spray on tablet in suitable equipment, such as, for example using conventional coating equipment in sugar production line, such as coating pan, porous container or fluid bed.Especially when liquid preparation is sprayed on tablet, the concentration of liquid is important.Therefore, in a specific embodiment, pharmaceutically acceptable liquid preparation has at most about 600mPa sec viscosity at a temperature of at most about 150 DEG C.

In addition, pharmaceutically acceptable liquid preparation generally has at least about 0 DEG C and at most about 250 DEG C, such as, e.g., from about 5 DEG C or more than 5 DEG C, such as, e.g., from about 10 DEG C or more than 10 DEG C, about 15 DEG C or more than 15 DEG C, about 20 DEG C or more than 20 DEG C, or about 25 DEG C or more than 25 DEG C of fusing point.When liquid preparation is heated or cooled while can load liquid preparation to tablet, fusing point is not very crucial.

Pharmaceutically acceptable liquid preparation can be based on water or it can be based on organic solvent or oil or oil sample material.Surprisingly, inventors have discovered that the tablet that the present invention is suitable to carrying can be immersed in the water, and (only need a few minutes or less time) when using water saturation, occur in that the tablet with cold and dry surface, i.e. water and suitable pharmaceutically acceptable liquid preparation can be used for based on aqueous liquid.

However, being to be included in based on the active material in aqueous or organic matter liquid to tablet loading in terms of paying close attention to more generally availability.This class I liquid I includes oil or oil sample material or pharmaceutically acceptable solvent.

This kind of oil or oil sample material can the groups selected from water, vegetable oil, hydrogenated vegetable oil and animal oil composition.

Suitable example includes apricot oil, apricot kernel oil, avocado oil, castor oil, coconut oil fat, cocoa butter, corn oil, cotton seed oil, grape seed oil, jojoba oil, Linseed oil, oleum maydis (maizeoil), olive oil, palm oil, peanut oil, persil oil, poppy seed oil, rape seed oil, sesame oil, soybean oil, sunflower oil, thistle-seed oil, walnut oil, wheat germ oil, butter, lard, tall oil, whale oil and its mixture.

Other examples are hydrophily oil or oil sample material, and they are selected from the group of following material composition：PTMEG class, such as, such as polyethylene glycols, polypropylene glycols；Polyoxyethylene；Polyoxypropylene class；Poloxamer class and its mixture；Or it can be selected from the group of following material composition：Xylitol, sorbierite, sodium potassium tartrate tetrahydrate, sucrose tribehenate, glucose, rhamnose, Lactitol, behenic acids, quinhydrones monomethyl ether, sodium acetate, ethyl fumarate, myristic acid, citric acid, Gelucire 50/13；Other Gelucire classes, such as, such as Gelucire 44/14, Gelucire 50/10, Gelucire 62/05, Sucr0- esters 7, Sucro- esters 11, Sucro- esters 15, maltose, mannitol and its mixture.

Oil or oil sample material can also be hydrophobicity oil or oil sample material, their groups selected from following material composition：Straight chain saturation alkane class, sorbitan ester class, paraffin；Fats and oil, such as, such as cocoa butter, butter, lard, polyethers ethylene glycol esters；Higher fatty acids, such as, such as stearic acid, myristic acid, palmitic acid；Higher alcohols, such as, such as cetanol, octadecanol；Low melt wax; such as, such as glycerin monostearate, glyceryl monooleate, hydrogenated fat, myristyl alcohol, octadecanol, substitution and/or unsubstituted monoglyceride class, substitution and/or unsubstituted two glyceride type, substitution and/or unsubstituted triglycerin esters, cera flava, cera alba, Brazil wax, castor wax, Japan tallow, acetylated monoglycerides class；NVP polymer, PVP polymer, acrylate copolymer or its mixture.

Suitable polyethylene glycols typically have about 400- about 35,000, such as, e.g., from about 800- about 35,000, about 1,000- about 35, the molecular weight of 000 scope, such as, such as polyethylene glycol 1,000, polyethylene glycol 2,000, polyethylene glycol 3,000th, polyethylene glycol 4,000, polyethylene glycol 5,000, Macrogol 6000, polyethylene glycol 7,000, polyethylene glycol 8,000th, polyethylene glycol 9,000, polyethylene glycol 10,000, polyethylene glycol 15,000th, polyethylene glycol 20,000 or polyethylene glycol 35,000.In some cases, it can use with about 35,000- about 100, the polyethylene glycol of 000 molecular weight.

In a specific embodiment, described oil or oil sample material can be the PEO with following molecular weight：About 2,000- about 7,000,000, such as, e.g., from about 2,000- about 100,000, about 5,000- about 75,000, about 10,000- about 60,000, about 15,000- about 50,000, about 20,000- about 40,000, about 100,000- about 7,000,000, such as, e.g., from about 100,000- about 1,000,000, about 100,000- about 600,000, about 100,000- about 400,000 or about 100,000- about 300,000.

The present invention can also use poloxamer class.Example includes other block copolymers of PLURONICS F87, poloxamer 237, Pluronic/Lutrol F 108 or poloxamer188 or oxirane and expoxy propane, such as PluronicAnd/or Tetronic

Series.Pluronic

The suitable block copolymer of series includes having about 3,000 or 3, more than 000, such as, e.g., from about 4,000- about 20,000 molecular weight and/or about 200- about 4,000cps, such as, the polymer of e.g., from about 250- about 3,000cps viscosity (Brookfield).Suitable example includes Pluronic

F38, P65, P68LF, P75, F77, P84, P85, F87, F88, F98, P103, P104, P105, F108, P123, F123, F127,10R8,17R8,25R5,25R8 etc..Tetronic

Serial suitable block copolymer includes having about 8,000 or 8, more than 000, such as, e.g., from about 9,000- about 35,000 molecular weight and/or about 500- about 45,000cps, such as, e.g., from about 600- about 40, the polymer of 000 viscosity (Brookfield).Above-mentioned viscosity be at 60 DEG C to be at room temperature the material of pasty state and at 77 DEG C to be at room temperature solid substance-measuring.

In another embodiment, described oily or oily-sample material is sorbitan ester, such as, such as sorbitan diisopstearate, sorbitan dioleate, sorbitan monolaurate, sorbitan list isostearate, dehydrated sorbitol mono-fatty acid ester, span 40, sorbitan monostearate, sorbitan sesquialter isostearate, NOFABLE SO-992, sorbitan sesquistearate, the isostearate of sorbitan three, sorbitan trioleate, sorbitan tristearate or its mixture.

Additionally or alternatively, described oil or oil sample material can be the mixture of different oil or oil sample materials, such as, the mixture or solvent or semisolid excipient class of such as hydrophily and/or lyophobic dust, such as propane diols；Polyglycolised (polyglycolised) glyceride type, including Gelucire 44/14；From the compound fat material of plant, including oleum theobromatis, Brazil wax；Plant oil, such as apricot kernel oil, coconut oil, corn oil, cotton seed oil, sesame oil, soybean oil, olive oil, castor oil, palm-kernel oil, peanut oil, rape oil, grape seed oil etc.；Hydrogenated vegetable oil, such as, such as hydrogenated groundnut, hydrogenated palm kernel oil, hydrogenated cottonseed oil, oil with hydrogenated soybean, rilanit special, hydrogenated coconut oil；From the natural fat acid substance of animal, including beeswax；Lanolin；Aliphatic alcohols, including cetanol, octadecanol, laruyl alcohol, myristyl alcohol, palmityl alcohol, stearic acid aliphatic alcohols；Esters, including tristerin, glycol stearate, ethyl oleate, isopropyl myristate；The semi-synthetic glyceride type of liquid ester exchange, including Miglycol810/812；Acid amides or fatty alkanol amide class, include diglycollic amide, the acetate esters of single and two-glyceride, the citric acid ester type of single and two-glyceride, the lactic acid ester of single and two-glyceride, single and two-glyceride, the polyglycereol esters of aliphatic acid, polyglycerol polyricinoleate, the propane diols esters of aliphatic acid, sorbitan list hard acid fat, sorbitan tristearate, stearoyl dilactic acid sodium, stearoyl dilactic acid calcium, the diacetyl tartaric acid ester class of single and two-glyceride etc. of stearmide ethanol, coconut fatty acid.

Pharmaceutically acceptable liquid preparation can also be dispersion, including：Emulsion；Micro emulsion, such as self-emulsifying microemulsion delivery system (SMEDDS)；Or suspension.

In general, the concentration of pharmaceutically acceptable liquid preparation in tablets is about 5%w/w or more than 5%w/w, such as, e.g., from about 10%w/w or more than 10%w/w, about 15%w/w or more than 15%w/w, about 20%w/w or more than 20%w/w, about 25%w/w or more than 25%w/w, about 30%w/w or more than 30%w/w, about 35%w/w or more than 35%w/w, about 40%w/w or more than 40%w/w, about 45%w/w or more than 45%w/w, about 50w/w or more than 50%w/w, about 60%w/w or more than 60%w/w or about 70% or more than 70%w/w.

The tablet that will be suitable for carrying loads the requirement of the tablet general satisfaction pharmacopeia obtained after pharmaceutically acceptable liquid preparation.Therefore, tablet of the invention typically has at least about 20N hardness and/or at most about 5%, such as, such as at most about 4%, at most about 3%, at most about 2%, at most about 1% or at most about 0.5% friability.

Liquid is caused substantially to be uniformly distributed in tablet additionally, it is contemplated that liquid is loaded into the tablet of the invention for being suitable to carrying.

Furthermore, it is possible to design the tablet for substantially discharging active material at once or with improved procedure.Typically there is the disintegration time of at most 15 minutes tested such as Ph.Eur to discharge the tablet of design at once, and thin membrane coated tablet can have the disintegration time of at most about 30 minutes.For improving the tablet of release, the release of active material has importance.

For the simple tablet of the present invention, in the dissolving-out method test according to USP, at least 75% treatment, prevention and/or diagnosis active material discharged in 30 minutes.

As described above, it is preferred to which embodiment is the tablet for being loaded with one or more treatments, prevention and/or diagnosis active material.

Effervescent tablet disintegration formulation principle

Inventors have discovered that the disintegration for the tablet for being loaded with lipophilic agents can not be improved by adding hydrophilic superdisintegrant, because disintegrant swelling character decline in liquid environment is caused.In this case, different disintegration principles can be applied based on effervescent effect.The disintegration of tablet is improved because the inside of carbon dioxide discharges.Effervescent tablet based on metal carbonate with and acid source combination.Metal carbonate is：Such as sodium acid carbonate, sodium carbonate, saleratus, potassium carbonate, calcium carbonate and concentrated crystal soda.Acid source is：Such as citric acid, Sodium citrate, DisodiumHydrogen Citrate, tartaric acid, malic acid, fumaric acid, sodium dihydrogen phosphate and sodium acid sulfite.Acid ingredient can not be included in tablets, because obtaining effervescent effect in vivo when tablet being dissolved in into acidic gastric juice and with metal carbonate reactant salt.

It is coated

By film coating tablet can also be given to be coated, such as, at once or improving release, enteric coating, improve release coating, protectiveness coating, anti-adhesive coatings etc..

Suitable coating material is：Such as methylcellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, acrylate copolymer, ethyl cellulose, Cellacefate, polyvinyl acetate phthalic acid ester, Hydroxypropyl Methylcellulose Phathalate, polyvinyl alcohol, sodium carboxymethylcellulose, cellulose acetate, Cellacefate, gelatin, methacrylic acid copolymer, polyethylene glycol, shellac, sucrose, titanium dioxide, Brazil wax, microwax, zein.

Plasticizer and other components can be added in coating material.Identical or different active material can also be added in coating material.

Fusing is coated

The hydrophobic surface that the present invention carries the tablet of fat can be prevented for the coating polymer adhesion in aqueous or organic solvent.Alternately, it is suitable using the fusing coating sprayed in molten form and solidify different lipophilic meltable lipids on the surface of the tablet using conventional coating equipment in sugar production line.Useful fusing coating substance is：Such as polyglycolised glycerides (Gelucire50/02, Gelucire 62/05, Gelucire 53/10), polyglyceryl palmitostearate, glyceryl behenate (ATO of Compritol 888), tristerin (Precirol WL), glyceryl palmito stearate (Precirol ATO 5), polyglycolised unsaturated glyceride class (Labrafil M1944).

Active material

In the context of the present invention, include can be to animal, such as treatment and/or prophylactic activity material, any biological and/or physiological activator that such as mammal, such as people are worked.The term includes material, protein, peptides, nutrients of drug substance, hormone, gene or gene order including antigen etc., such as vitamin, mineral, lipid and carbohydrate and its mixture.Therefore, the term is included in the disease or obstacle for the treatment of and/or prevention influence animal or people or has the material of application in any animal of regulation or human physiology condition.The term is additionally included in when being administered with effective dose has effective any bioactive substance to living cells or organism.

Example suitable for the active material of Tablets is mainly any active material, such as, for example freely water solubility and more slightly soluble or insoluble active material.Therefore, the example of relevant active material for being suitable for application is：Such as antibacterial material, antihistaminic and decongestant, anti-inflammatory agent, antiparasitic, antiviral agent, local anesthetic, antifungal, amoebicidals or trichomonacide (trichomonocidal agents), anodyne, anxiolytic, anticoagulation, anti-arthritic, antiasthmatics, anti-arthritic, anti-coagulants, anticonvulsant, antidepressants, antidiabetic, Betimol, antimalarial, antimicrobial, antineoplastic, slimming drugs, antipsychotic drug, antihypertensive, antitussive, autoimmune disorders activating agent, Alibra, antiparkinsonism medicine, anti-Alzheimer disease medicine, alexipyretic, anticholinergic drug, anti-ulcer agent, anoretics, receptor blocking agent, β -2 activators, beta-agonists, hypoglycemic agent, bronchodilators, Central nervous system has effective activating agent, cardiovascular drug, cognitive accelerator, contraceptive, gemfibrozil, cytostatics, diuretics, bactericide, H-2 retarding agents, hormone drug, hypnotic, influence convergent force medicine, muscle relaxant, contraction of muscle medicine, excitant medicine, sedative, sympathetic transmitter releasers, vasodilator agent, vasoconstrictor, tranquillizer, electrolyte replenisher, vitamin, counter-stimulus, stimulant, anti- hormone, Drug Antagonists, lipid regulating agent, uricosuric, cardiac glycoside, expectorant, cathartic, contrast agent, radiopharmaceutical, developer, peptides, enzyme, growth factor etc..

Instantiation includes：For example

Anti-inflammatory agent class, such as brufen, Indomethacin, naproxen, nalorphine；

Antiparkinsonism medicine class, such as bromocriptine, biperidin, benzhexol, benzatropine；

Antidepressants class, such as imipramine, nortriptyline, pritiptyline；

Antibioticses, such as clindamycin, erythromycin (erythomycin), Fusidic Acid, gentamicin, mupirocin, amfomycin, neomycin, metronidazole, ayerlucil, bacitracin, actiline, polymyxin B, acitromycin；

Antifungal class, such as Miconazole, ketoconazole, clotrimazole, amphotericin B, nystatin, mepyramine, econazole, Fluconazole, Flucytosine (flucytocine), griseofulvin, bifonazole, Amorolfine (amorofine), nystatin, Itraconazole, terbenafine, terconazole, Tolnaftate；

Antimicrobial class, such as metronidazole, Tetracyclines, terramycin class (oxytetracylines), penicillins (peniciilins)；

Antiemetic class, such as Metoclopramide, droperidol, haloperole, fenazil；

Antihistaminic, such as chlorphenamine, RMI 9918, triprolidine；

Antimigraine class, such as dihydroergotamine, ergotamine, pizofylline；

Coronal, brain or peripheral vasodilator class, such as nifedipine, diltiazem；

Antianginal drug, such as, such as nitroglycerin, ISDN, molsidomine, Verapamil；

Calcium channel blocker class, such as Verapamil, nifedipine, diltiazem, nicardipine；

Hormone drug class, such as estradiol, oestrone, estriol, Polyestradiol, poly- estriol, dienestrol, diethylstilbestrol, progesterone, dihydroprogesterone, cyproterone, DANAZOL, testosterone；

Contraceptive class, such as ethinylestradiol, lynestrenol, Etynodiol, norethindrone, mestranol, norgestrel, Levonorgestrel, Desogestrel (desodestrel), Medroxyprogesterone；

Antithrombotic drug class, such as heparin, warfarin；

Diuretics class, such as Hydrochioro, flunarizine, minoxidil；

Antihypertensive class, such as inderal, metoprolol, clonidine, pindolol；

Cortical steroid, such as beclomethasone, betamethasone, betamethasone -17- valerates, dipropium dipropionate, clobetasol, Clobetasol 17-butyrate, Clobesol, desonide, desoximetasone, dexamethasone, diflucortolone, aniprime, neopentanoic acid dexamethasone, FA, fluocinoide, hydrocortisone, hydrocortisone -17- butyrates, hydrocortisone buteprate, methylprednisolone, Triamcinolone acetonide, hacinonide, fluprednidene acetate (fluprednide acetate), alklometasone-dipropionate, fluocortolone, fluticasone propionate (fluticason-propionte), momestasone furoate, desoximetasone, diflurason-diacetate, Halquinol, cliochinol, chlorchinaldol, FA etc.；

Dermatological Agents class, such as furantoin, Dithranol, clioquinol, hydroxyl quinoline, isotretionin, Methoxsalen, methotrexate (MTX), tretionin, trioxalen, salicylic acid, penicillamine；

Steroid, such as estradiol, progesterone, norethindrone, Levonorgestrel, Etynodiol, D-Norgestrel (levonorgestrol), norgestimate, gestanin, Desogestrel, 3- ketone-Desogestrel (desogesterel), demegestone, promethoestrol, testosterone, spirolactone and its esters；

Nitro compound species, such as isoamyl nitrite, nitroglycerine and ISDN；

Opiates, such as morphine, buprenorphine, Oxymorphone, Hydromorphone, codeine, C16H25NO2；

Prostaglandin, such as, such as the member in PGA, PGB, PGE or PGF series, such as, such as minoprostol, dinoprostone, Carboprost, eneprostil；

Peptides, such as somatotropin releasing factor, growth factor (such as EGF (EGF), nerve growth factor (NGF), TGF, PDGF, insulin-like growth factor (IGF), fibroblast growth factor (aFGF, bFGF etc.), growth hormone release inhibiting hormone, calcitonin, insulin, pitressin, interferon, IL-2 etc., urokinase, serratiopeptidase, superoxide dismutase, thyrotropin-releasing hormone (TRH), luteinizing hormone-releasing hormone (LH-RH), corticotropin releasing hormone, growth hormone releasing hormone (GHRH), oxytocin, erythropoietin(EPO) (EPO), colony stimulating factor (CSF) etc.；

Other active materials of concern include ubiquinone (Coenzyme Q10)；Omega-fatty acid, including the fish oil containing this kind of aliphatic acid；Statins, including Simvastatin, Lovastatin, Atorvastatin, Pravastatin, Pravastatin, rosuvastatin etc.；Fenofibrate.

Significant example also has prescription medicine class：

Cardiovascular drug

Zocor

、Lipitor

、Prevachol

、Mevalotin

、Mevacor

、Lescol

、TriCor、Norvasc, Cozaar and Hyzaar

, Prinivil and Prinzide、Diovan

/Co-Diovan

、Zestril

、Vasotech

And Vaseretic、Lotensin

/Cibacen

And Lotrel

、Adalat

、Toprol-XL/Seloken、Tritace

/Delix

、Accupril

And Accuretic

、Avapro

And Avalide

、Plendil

、Monopril

、Blopress

、Atacand

、Tenormin

、Avapro/Aprovel、Coreg

、Altace

、Capoten

、Plavix

、Lovenox

/Clexane

、Fraxiparine

、ReoPro、Panaldine

、Cordarone

Medicine for central nervous system

Paxil/Seroxat

、Zolotoft

、Prozac

、Prozac Weekly

And Sarafem、Effexor

、Wellbutrin、Celexa

、Remeron

、Serzone

、Zyprexa

、Risperdal

、Seroquel

、Clozaril/Leponex

、Neurontin

、Depaktoke

、Lamictal

、Topamax

、Tegretol

、Imitrex

/Imigran

、Zomig

、Maxalt

、Ambien、Stilnox

、Ultane

/Sevorane

、Diprivan

、BuSpar、Xanax

、Aricept

、Memantine

、Adderall

、Dystonia

、Botox

；

Anti-infectious agent

Augmentin

、Cipro

/Ciprobay

、Zithromax

、Biaxin

、Levaquin

And Floxin

、Rocephin

、Primaxin

、Ceftin

/Zinnat

、Cravit

、Zosyn

/Tazocin

、Cefzil

、Tequin

、Tortaz/Fortum

、Combivir

、Zerit

、Valtrex、Epivir

、Zovirax

、Crixivan

、Viracept

、Viramune

、Kaletra

、Diflucan

、Lamisil

、Sporanox

Medicine for respiratory system

ClaritinAllegra、Telfast

、Zyrtec、Flonase

/Flixonase

、Atrovent

、Nasonex

、Rhinocort

、Alesion

、Singulair

、Flovent

/Flixotide

、Advair

/Seretide

、Serevent

、Pulmicort

、Ventoline

、Combivent

、Synagis

、Mucosolvan

；

Gastrointestinal drug

Prilosec

/Losec

、Prevacid

、Gaster

、Takepron

、Zantac、Pantozol、Nexium、Protonix

、Aciphex

/Pariet

、Pepcid、Axid

、Zoton

、Zofran

Cancer drug

Taxol

、Taxotere

、Nolvadex

、Herceptin、Ellence

/Pharmorubicin

、Lupron

、Zoladex

、Leuplin

、Casodex

、Intron A

、Peg-Intron

And Rebertron

、Rituxan、Gemzar

、Paraplatin

、Camptosar

Anti-arthritic/anodyne

Celebrex

、Vioxx

、Enbrel

、Remicade

、Voltaren

、Mobic

Duragesic

Ultram

And Ultrcet

Treating hematopathy

Procrit

/Eprex

、Epogen

、Epogin

、NeoRecormon

、

Neupogen、NovoSeven

Rezulin

Glucophage

、Humulin Avandia

、Humalog

、Actos

、Amaryl

、Glucovance

、Glucophage XR

、Glucotrol XL

、Precose

/Glucobay

Bone m etabolism conditioning agent

Fosamax

、Evista

、Miacalcin

、Actone

1、Aredia

Urethra disorders medicine

Harnal

、Proscar

、Cardura

、Flomax

、Detrol

Hormone

Premarin

、Premphase

And prempro、Estraderm

、Synthroid

Immunodepressant

Neoral

/Sandimmun

、CellCept、Rapamune

, tacrolimus, such as Prograf

、Medrol

Multiple sclerosis medicine

Avonex

、Betaseron/Betaferon、Rebif

、Copaxone

Biological products

Prevnar

、Engerix-B

、Infanrix

、Gamimune N

Sex dysfunction medicine

Viagra

Developer

Iopamiron

、Omnipaque

、Magnevist

Ophthalmic medicine

Xalatan

、TrusoptAnd Cosopt

Dept. of dermatology's medicine

Accutane

/Roaccutan

、Cleocin

Grow not pedicure

Genotropin、Humatrope

Infertility medicine

Gonal-F、Follistim(Puregon

Dagger-axe thanks to (Gaucher) sick medicine

Cerezyme

Slimming drugs

Xencial

Acromegalia medicine

Sandostatin

Contraceptive

Depo-Provera

。

Other significant examples of slightly soluble, indissoluble or water insoluble active material are as shown in following table：

Table 1

Insoluble medicine candidate

Medicine name	Treat type	Dissolubility in water
			Alprazolam amiodarone Amlodipine astemizole atenolol imuran azelastine beclomethasone budesonide buprenorphine butalbital carbamazepine carbidopa CTX cefalexin Cholestyramine Ciprofloxacin Cisapride cis-platinum CLA Clonazepam Clozapine	The anti-infective cardiovascular anti-infective anti-infective CNSCNS of stomach and intestine anticancer of the cardiovascular anticancer breathing breathing breathing CNSCNSCNSCNS of CNS angiocarpy cardiovascular-respiratories	The insoluble slightly soluble slightly soluble of the insoluble insoluble slightly soluble of insoluble slightly soluble indissoluble (sparingly) slightly soluble of insoluble insoluble indissoluble (sparingly) slightly soluble of the insoluble slightly soluble of insoluble atomic molten slightly soluble

(continuing)

Medicine name	Treat type	Dissolubility in water
			Cyclosporin diazepam diazepam sodium digoxin Dipyridamole divalproex sodium dobutamine Doxazosin enalapril estradiol Etodolac Etoposide famotidine felodipine citric acid fentanyl fexofenadine Finasteride Fluconazole Flunosolide Flurbiprofen Fluvoxamine frusemide Glipizide glibenclamide brufen ISDN isotretinoin isradipine Itraconzole ketoconazoles	The antimycotic cardiovascular skin diseases of breathing NSAIDCNS Cardiometabolics metabolism NSAID of the cardiovascular cardiovascular hor-mone NSAID anticancers intestines and stomach angiocarpy CNS breathing urogenitals of immunodepressant CNSNSAID angiocarpy angiocarpy CNS are cardiovascular antimycotic	The insoluble indissoluble of the insoluble indissoluble of the insoluble slightly soluble indissoluble of the insoluble slightly soluble of the insoluble indissoluble slightly soluble of the insoluble atomic molten slightly soluble of the insoluble slightly soluble slightly soluble indissoluble slightly soluble indissoluble of actually insoluble slightly soluble indissoluble is insoluble
Ketoprofen	NSAID	Slightly soluble

(continuing)

Medicine name	Treat type	Dissolubility in water
			Lamotrigine Lansoprazole Loperamide Loratadine Lorazepam Lovastatin Medroxyprogesterone mefenamic acid methylprednisolone midazolam Mometasone Nabumetone naproxen nicergoline nifedipine Norfloxacin Omeprazole taxol phenytoinum naticum piroxicam quinapril Ramipril Risperidone inverase Sertraline Simvastatin Terbinafine RMI 9918 fluoxyprednisolone valproic acid zolpidem	The cardiovascular antimycotic breathing steroids CNSCNS of the cardiovascular angiocarpy CNS proteinase inhibitor Cs NS of the CNS intestines and stomach intestines and stomach breathing CNS cardiovascular anti-infective intestines and stomach anticancer CNSNSAID of cardiovascular hor-mone analgesic steroid anesthesia steroids NSAIDNSAIDCNS	The insoluble slightly soluble indissoluble of the insoluble slightly soluble slightly soluble of the insoluble insoluble actually insoluble slightly soluble of the insoluble indissoluble of the insoluble insoluble actually insoluble slightly soluble slightly soluble of the insoluble slightly soluble of the insoluble slightly soluble of slightly soluble

Table 2

Insoluble medicine with low bioavilability

Medicine name	Indication	Dissolubility in water	Bioavilability
				Astemizole cyclandelate perphenazine testosterone famotidine budesonide Mesalazine clemastine fumarate buprenorphine Sertraline Anranofin felodipine isradipine DANAZOL Loratadine ISDN fluphenazinum spirolactone Biperiden cyclosporin Norfloxacin Cisapride Nabumetone Dronabinol Lovastatin Simvastatin	Allergic rhinitis peripheral artery disease phrenoblabia androgen replacement GERD allergic rhinitis IBS allergic rhinitis pain anxiety arthritis hypertension hypertension mullerianosis allergic rhinitis angina pectoris phrenoblabia hypertension, oedema Parkinson's transplanting bacterium infection GERD arthritis antiemetic hyperlipemias	The insoluble indissoluble slightly soluble slightly soluble of the insoluble indissoluble of insoluble slightly soluble indissoluble slightly soluble slightly soluble slightly soluble slightly soluble slightly soluble is insoluble insoluble	Low-intermediate is low, (39-50%) is low, (~15%) is low, (~20%) is low, (~39%) is low, (＜ 30%) is low, (＜ 44%) is low, (15-25%) is low, (15%) it is low, (15-24%) is low low, (20-35%) is low, (2-3%) is low, (2 5%) is low, (29-33%) is low, (30%) it is low, (30-40%) is low, (35-40%) is low, (35%) low 10-20%) it is low, (~5%) is low, (＜ 5%)

The amount of the active material of incorporation tablet can be selected according to known pharmaceutical preparation principle.The dosage that generally, there are the active material in Tablets depends especially on specific drug substance, the age of patient and the state of an illness and the disease treated.

In the specific embodiment of the present invention, described treatment, prevention and/or diagnosis active material is solid at ambient temperature.However, this is not absolute requirement, it can also be liquid at room temperature.Active material can also exist with dispersion of the active material in pharmaceutically acceptable liquid preparation, or active material can exist with emulsion, including SMEDD (self-emulsifying microemulsion delivery system) form.

As described above, active material can be scattered in pharmaceutically acceptable liquid preparation.In a specific embodiment, active material is at least partially soluble in pharmaceutically acceptable liquid preparation and/or its at least part and existed with amorphous.

The other side of the present invention

The invention further relates to prepare the method for tablet, comprise the following steps：

I) tablet for being suitable to carrying as any one of claim 1-32 is prepared, the tablet optionally includes one or more treatments, prevention and/or diagnosis active material；

Ii the pharmaceutically acceptable liquid preparation loaded obtained from the step i) tablet for being suitable to carrying as any one of claim 33-59) is given, the liquid preparation optionally includes one or more treatments, prevention and/or diagnosis active material, and the load time is to be enough the time limit with the tablet for being suitable to carrying described in described pharmaceutically acceptable liquid preparation saturation.

Optionally include the pharmaceutically acceptable liquid preparations of one or more treatments, prevention and/or diagnosis active material to the tablet loading for being suitable to carrying by spraying, or the process is placed in the excessive pharmaceutically acceptable liquid preparation for optionally including one or more treatments, prevention and/or diagnosis active material by will be suitable for the tablet of carrying and carried out.

In the above-mentioned methods, for the amount of the tablet for being suitable to carry equivalent to 1kg, step ii) in time limit at most about 60 minutes, such as, such as at most about 45 minutes or at most about 30 minutes (and being corresponding time limit for the batch that another weight exceedes 1kg).

The present invention is explained further in following non-limiting examples.

Embodiment

Embodiment 1

Preparation and its characteristic suitable for the tablet of carrying

Based on (the silica of substance A eroperl 300 for absorbing oil, Degussa), NeusilinUS2 (Neusilin US2s, Fuji Chemical Industry) Avicel (microcrystalline celluloses,) and Fujicalin SG FMC, (anhydrous Bibasic Calcium Phosphate, Fuji Chemical Industry) prepares 6 kinds of tablet compositions.

Composition 1

Neusilin US2 99%

Magnesium stearate 1%

Composition 2

Avicel PH102 99%

Magnesium stearate 1%

Composition 3

Aeroperl 300 80%

PEG 6,000 19%

Magnesium stearate 1%

Composition 4

Aeroperl 300 55%

Avicel PH 101 44%

Magnesium stearate 1%

Composition 5

Avicel PH 102 99%

Magnesium stearate 1%

Composition 6

Fujicalin 99%

Magnesium stearate 1%

Magnesium stearate and remaining composition are blended 3 minutes in Turbula blender.The compressed tablets on single punch presses Diaf TM20.Tablet size：9mm circle compound cups.

Tablet is put into corn oil 24 hours.Oil was fully absorbed in the 1st hour.

Tablet loading Imwitor 308, Sasol (Capmul MCM C8) and the Simvastatin of 10% dissolving to composition 5.Equivalent to 40 DEG C more than the fusing points of Imwitor 308 (m.p.35 DEG C) at a temperature of carry out the loading of oil.

Composition 1.

Tablet number	Plate core weight, mg	The oily mg that label is included	The oil of absorption, mg	The oily % of absorption
					1	142	367	225	61.3
2	139	364	225	61.8
					3	143	369	226	61.2
4	144	367	223	60.8
					5	142	370	228	61.6
6	150	370	220	59.5
					Average value	143	368	224.5	61.0

The oil absorption of tablet of the table 1. containing Neusilin US2.(composition 1) determines tablet hardness by Schleuninger 8M tablet hardnesses tester.

Mean tablet hardness before loading oil, N	Mean tablet hardness after loading oil, N
		38	34

Table 2. loads the tablet hardness (composition 1) before and after oil

Disintegration time has exceeded 24 hours before and after loading oil.

By add concentration be 1% Ac-di-sol by disintegration time be down to less than 15 minutes (before loading) and oil load after be down to 5 hours.Ac-di-sol (AC-DI-SOL, FMC) is the superdisintegrant for the oily absorbability for not influenceing Neusilin.

Based on tablet density p_tWith " real density " ρ of component_sCalculate the porosity of tablet before loading.The porosity ε of tablet is calculated according to equation 1.

$\mathrm{\ϵ}=1-\frac{{\mathrm{\ρ}}_t}{{\mathrm{\ρ}}_s}$ Equation 1

The ratio between weight of the density of tablet based on tablet and volume." real density " of component measures density based on the gas balloon determined using Micromeritics Accupyc 1330 in helium.

The corn oil maximum load ability based on weight is calculated according to equation 2.

Load capability $w/w\%=\frac{\mathrm{\ϵ}}{\mathrm{\ϵ}+(1-\mathrm{\ϵ})\frac{{\mathrm{\ρ}}_s}{{\mathrm{\ρ}}_1}}100$ Equation 2

The density p of corn oil₁=0.92g/cm³

The porosity % of tablet	Maximum oil load capability %	The oily loading capacity % of measure
			80	63	61

The application (composition 1) of the oily load capability of table 3..

Composition 2

Tablet number	Plate core weight, mg	The oily mg that label is included	The oil of absorption, mg	The oily % of absorption
					1	232	349	117	33.52

Tablet number	Plate core weight, mg	The oily mg that label is included	The oil of absorption, mg	The oily % of absorption
					2	229	351	122	34.76
3	230	351	121	34.47
					4	229	349	120	34.38
5	229	353	124	35.13
					6	230	349	119	34.10
Average value	230	350	121	34.39

Oily absorbability (composition 2) of the table 4. containing Avicel

Tablet hardness is determined by Schleuninger 8M tablet hardnesses tester.

Mean tablet hardness before loading oil, N	Mean tablet hardness after loading oil, N
		33	32

Table 5. loads the tablet hardness (composition 2) before and after oil

The porosity % of tablet	Maximum oil load capability %	The oily loading capacity % of measure
			48	35	34

The application (composition 2) of the oily load capability of table 6.

Composition 3

Tablet number	Plate core weight, mg	The oily mg that label is included	The oil of absorption, mg	The oily % of absorption
					1	105	222	117	52.7
2	108	226	118	52.2
					3	113	230	117	50.9
4	106	228	122	53.5
					5	126	232	106	45.7
6	110	227	117	51.5
					Average value	111.3	227.5	116.2	51.1

The oily absorbability (composition 3) of tablet of the table 7. containing Aeroperl/PEG 6000 determines tablet hardness by Schleuninger 8M tablet hardnesses tester.

Mean tablet hardness before loading oil, N	Mean tablet hardness after loading oil, N
		15	10

Table 8. loads the tablet hardness (composition 3) before and after oil

The porosity % of tablet	Maximum oil load capability %	The oily loading capacity % of measure
			70	54	51

The application (composition 3) of the oily load capability of table 9.

Composition 4

Tablet number	Plate core weight, mg	The oily mg that label is included	The oil of absorption, mg	The oily % of absorption
					1	192	324	132	40.7
2	198	329	131	39.8
					3	204	329	125	38.0
4	193	325	132	40.6
					5	193	325	132	40.6
Average value	196	326	130	39.9

The oily absorbability (composition 4) of tablet of the table 10. containing Aeroperl/Avicel

Mean tablet hardness before loading oil, N	Mean tablet hardness after loading oil, N
		30	27

Tablet hardness (composition 4) before and after the oil loading of table 11.

Mean disintegration time before loading oil, minute	Mean disintegration time after loading oil, minute
		2	1

Table 12. loads the disintegration time (composition 4) of the tablet before and after oil

Compared with composition 3, tabletting characteristics and tablet hardness are improved by adding Avicel PH101 rather than PEG 6000.

Composition 5

Tablet number	Plate core weight, mg	The oily mg that label is included	The oil of absorption, mg	The oily % of absorption
					1	229	338	109	32.2
2	229	337	108	32.0
					3	229	337	108	32.0
4	229	339	110	32.4
					5	230	338	108	31.9
6	229	337	108	32.0
					7	229	338	109	32.2
8	229	338	109	32.2
					9	229	339	110	32.4
10	228	339	111	32.7
					11	230	340	110	32.4
12	230	338	108	31.9
					Average value	229	338	109	32.2

Table 13. contains the oily absorbability (composition 5) of tablet for the Avicel for being loaded with solution of 10% Simvastatin in Imwitor 308

Mean tablet hardness before loading oil, N	Mean tablet hardness after loading oil, N
		35	32

Table 14. is loaded with the tablet hardness (composition 5) before and after solution of 10% Simvastatin in Imwitor 308

Mean disintegration time before loading oil, minute	Mean disintegration time after loading oil, minute
		1	2

Table 15. loads the tablet disintegration times (composition 5) before and after oil

Composition 6

Tablet number	Plate core weight, mg	The oily mg that label is included	The oil of absorption, mg	The oily % of absorption
					1	258	383	125	48.4
2	259	384	125	48.3
					3	259	383	124	47.9
4	260	383	123	47.3

Tablet number	Plate core weight, mg	The oily mg that label is included	The oil of absorption, mg	The oily % of absorption
					5	257	382	125	48.6
6	261	384	123	47.1
					Average value	259	383.2	124.2	47.9

Table 17. contains oily absorbability (composition 6) of the tablet for the Fujicalin for being loaded with corn oil

Mean tablet hardness before loading oil, N	Mean tablet hardness after loading oil, N
		42	20

Table 18. is loaded with the tablet hardness (composition 6) before and after corn oil

Mean disintegration time before loading oil, minute	Mean disintegration time after loading oil, minute
		2	6.1

Table 19. is loaded with the tablet disintegration times (composition 6) before and after corn oil

Conclusion

Porous tablet may be used as the carrier of oil formulation, described oil formulation such as oil, emulsion, micro emulsion and liquefied semisolid, including be used as drug substance that is liquid form or being dissolved or dispersed in liquid-carrier at an elevated temperature.Oil can be applied on tablet by conventional coating technology (roller, porous container or fluid bed).The feed rate of oil should be adjusted so that equilibrium oil is absorbed into the speed of label.

According to the oily absorbability of the porosity measurement of label.Tablet space is filled close to saturation with oil.

It is applicable to provide the arbitrary substance of the tablet of 30-90% scope porositys.Other non-above-mentioned materials may be used as tablet core material, such as calcium carbonate, magnesia, the material of the spray drying preferably with gratifying mobility and high-specific surface area.Tablet disintegration times can be adjusted by adding convas tablet disintegrant and for preparing release tablet and controlled release matrix tablet at once.

It is loaded with the embodiment (APIs) of the porous tablet of active material

Embodiment 2

The specification of label

Neusilin US2   93mg

Magnesium stearate 1mg

Mean tablet hardness： 52N

Tablet diameters：8mm (compound cup)

The compressed tablets on single punch presses Diaf TM20.

Load the specification (1mg tacrolimus) of piece

At ambient temperature with concentration is dissolved in polyethylene glycol 400 and is sprayed on Neusilin US2 labels for 0.95% tacrolimus in coating vessel.The composition of the 1mg tablets of loading as shown in table 1, piece weight, the carrier loading capacity equivalent to 53%w/w is loaded equivalent to 200mg.

Mean tablet hardness：52N

Material	mg
		Tacrolimus	1.00
PEG 400	105.0
		Neusilin US 2	93

Material	mg
		Magnesium stearate	1
Amount to	200

Table 20. is loaded with the 1mg tablet compositions of solution of the tacrolimus in PEG400.

Embodiment 3

The specification of label

Neusilin US2      198mg

Magnesium stearate 2mg

Mean tablet hardness：    42N

Tablet diameters：10mm (compound cup)

The compressed tablets on single punch presses Diaf TM20.

Load the specification (20mg Atorvastatins) of piece

Concentration is dissolved in the Imwitor 308 (Capmul MCM C8) of fusing for 10% Atorvastatin at 40 DEG C and is sprayed in coating vessel on the Neusilin US2 labels for being heated to 35 DEG C.Loading piece is cooled down so as to solidified carrier in refrigerating box after loading.

The 20mg tablet compositions of loading as shown in table 2, piece weight, the carrier loading capacity equivalent to 50%w/w are loaded equivalent to 400mg.

Mean tablet hardness：48N

Material	mg
		Atorvastatin	20.0
Imwitor 308	180.0
		Neusilin US 2	198.0
Magnesium stearate	2.0
		Amount to	400.0

Table 21. is loaded with the 20mg tablet compositions of solution of the Atorvastatin in Capmul MCM C8.

Embodiment 4

The specification of label

Neusilin US2    351mg

Magnesium stearate 2mg

Mean tablet hardness：  60N

Figure of tablet：9 × 19mm of oblong tablet

The compressed tablets on single punch presses Diaf TM20.

Load the specification (145mg fenofibrates) of piece

The fenofibrate that concentration is 35% is dissolved in the mixture (70: 30) of the Macrogol 6000 of fusing and PLURONICS F87 and is sprayed at a temperature of 80 DEG C and is heated in coating vessel on the Neusilin US2 labels of 70 DEG C of temperature.Loading piece is cooled to the temperature of the fusing point (60 DEG C) less than PEG and poloxamer after loading in refrigerating box.

The 145mg tablet compositions of loading as shown in table 3, piece weight, the carrier loading capacity equivalent to 54%w/w are loaded equivalent to 767mg.

Mean tablet hardness：57N

Material	mg
		Fenofibrate	145.0
PEG6000	188.4
		PLURONICS F87	80.8
Neusilin US2	350.8
		Magnesium stearate	2.0
Amount to	767.0

Table 22. is loaded with the 145mg tablet compositions of solution of the fenofibrate in the fusion mixture (70: 30) of PEG 6000 and PLURONICS F87

Embodiment 5

The specification of label

Neusilin US2  84mg

Magnesium stearate 1mg

Mean tablet hardness：42N

Tablet diameters：7mm (compound cup)

The compressed tablets on single punch presses Diaf TM20.

Load the specification (10mg Simvastatins) of piece

Concentration is dissolved in (MCT) Viscoleo on Neusilin US2 cores for 10% Simvastatin in coating vessel.The 10mg tablet compositions of loading as shown in table 4, piece weight, the carrier loading capacity equivalent to 54%w/w are loaded equivalent to 185mg.

Material	mg
		Simvastatin	10.0
Glyceryl monolaurate	89.9
		Neusilin US 2	84.1
Magnesium stearate	1.0
		Amount to	185.0

Table 23. is loaded with the 10mg tablet compositions of solution of the Simvastatin in Viscoleo

Embodiment 6

To neusilin tablets loading Viscoleo (medium chain triglycerides)

Tableting processes

Neusilin tablets are suppressed on single punch presses Diaf TM20：

Tablet properties before loading

Tablet diameters：9mm

Figure of tablet：Compound cup

Piece weight：134mg

Tablet weight variation, S_rel：1.6%

Tablet hardness：51N (is determined) using hardness-testing device Schleuniger M8

Loading procedure (loading process)

The coating part with top jet nozzle is used to load viscoleo to 50g tablets in the fluid bed Phast FB100 of laboratory scale.

Atomization air flow：1m³/ hour

Fluidize air-flow：40m³/ hour

Liquid feeding speed：2.5g minute

Until the Coating times of tablet saturation：30 minutes

Weight increase：67.5g viscoleo.

Tablet properties after loading

Piece weight：305mg (loading capacity 56w/w%)

Tablet hardness：51N

Tablet weight variation, S_rel：5.1%

Conclusion

It is practicable for liquid preparation is loaded on porous tablet within short process time as the conventional coating equipment in sugar production line of fluid bed.These tablets quickly absorb the liquid applied on the surface of the tablet by spray.The tablet hardness influence that liquid body is not loaded.When mixing active material, weight differential increases to 5.2% from 1.6%, still falls within the acceptable limit related to dose variation.

Claims (65)

1. the tablet for being suitable to carrying with 30%v/v or more than 30%v/v porositys, drug carrier composition as pharmaceutically acceptable liquid preparation, the wherein tablet there is 20N or more than 20N hardness and contain at least 60% concentration alumina silicate as provide porosity excipient.

2. the tablet for being suitable to carrying of claim 1, wherein the alumina silicate is magnesium aluminometasilicate.

3. the tablet for being suitable to carrying in claim 2, wherein described alumina silicate is

4. the tablet for being suitable to carrying in claim 3, wherein the alumina silicate is

5. any one of the claim 1-4 tablet for being suitable to carrying, wherein providing the excipient of porosity more than 70%w/w or 70%w/w concentration to exist.

6. any one of the claim 1-4 tablet for being suitable to carrying, wherein providing the excipient of porosity more than 80%w/w or 80%w/w concentration to exist.

7. any one of the claim 1-4 tablet for being suitable to carrying, wherein providing the excipient of porosity more than 90%w/w or 90%w/w concentration to exist.

8. any one of the claim 1-4 tablet for being suitable to carrying, wherein providing the excipient of porosity more than 95%w/w or 95%w/w concentration to exist.

9. any one of claim 1-4's is suitable to the tablet of carrying, wherein cause tablet to be loaded with least 20%w/w corn oil when test as described herein, the gross weight of solid dosage forms during based on loading.

10. any one of the claim 1-4 tablet for being suitable to carrying, wherein tablet has 25N or more than 25N hardness.

11. any one of the claim 1-4 tablet for being suitable to carrying, with 5% or less than 5% friability.

12. any one of the claim 1-4 tablet for being suitable to carrying, it is inert to treat.

13. the tablet for being suitable to carrying of claim 12, is made up of the inert pharmaceutically acceptable excipient of one or more.

14. any one of claim 1-4 or the tablet described in claim 13, are loaded with pharmaceutically acceptable liquid preparation, its concentration is 20%w/w or more than 20%w/w, the gross weight of solid dosage forms during based on loading.

15. the tablet of claim 14, wherein the presence concentration of pharmaceutically acceptable liquid preparation is 40%w/w or more than 40%w/w, the gross weight of solid dosage forms during based on loading.

16. the tablet of claim 15, wherein pharmaceutically acceptable liquid preparation has at most 600mPa sec viscosity at a temperature of 150 DEG C of highest.

17. the tablet of claim 15, wherein pharmaceutically acceptable liquid preparation has the fusing point of at least 0 DEG C and 250 DEG C of highest.

18. the tablet of claim 17, wherein pharmaceutically acceptable liquid preparation has 5 DEG C or more than 5 DEG C of fusing point.

19. the tablet of claim 15 or 18, wherein pharmaceutically acceptable liquid preparation is oil or oil-sample material.

20. the tablet of claim 15 or 18, wherein pharmaceutically acceptable liquid preparation is pharmaceutically acceptable solvent.

21. the tablet of claim 19, wherein described oily or oily-sample material is selected from the group of water, vegetable oil, hydrogenated vegetable oil and animal oil composition.

22. the tablet of claim 21, wherein described oily or oily-sample material is selected from the group of apricot oil, almond oil, avocado oil, castor oil, coconut oil fat, cocoa butter, corn oil, cotton seed oil, grape seed oil, jojoba oil, Linseed oil, oleum maydis, olive oil, palm oil, peanut oil, poppy seed oil, rape seed oil, sesame oil, soybean oil, sunflower oil, thistle-seed oil, walnut oil, wheat germ oil, butter, lard, tall oil, whale oil and its mixture composition.

23. the tablet of claim 21, wherein described oily or oily-sample material is hydrophily oil or oil-sample material, the group of hydrophily oil or oil-sample material selected from following material composition：PTMEG class；Polyoxyethylene；Polyoxypropylene class；Poloxamer class；And its mixture；Or hydrophily oil or oil-sample material are selected from the group of following material composition：Xylitol, sorbierite, sodium potassium tartrate tetrahydrate, sucrose tribehenate, glucose, rhamnose, Lactitol, behenic acids, quinhydrones monomethyl ether, sodium acetate, ethyl fumarate, myristic acid, citric acid, Gelucire 50/13, other Gelucire classes, Sucro- esters 7, Sucro- esters 11, Sucro- esters 15, maltose, mannitol and its mixture.

24. the tablet of claim 23, wherein described PTMEG class is selected from polyethylene glycols and polypropylene glycols.

25. the tablet of claim 23, wherein described other Gelucire classes are selected from Gelucire44/14, Gelucire 50/10 and Gelucire 62/05.

26. the tablet of claim 21, wherein described oily or oily-sample material is hydrophobicity oil or oil-sample material, the group of hydrophobicity oil or oil-sample material selected from following material composition：Straight chain saturation alkane class, sorbitan ester class, paraffin；Fats and oil；Higher fatty acids；Higher alcohols；Low melt wax；NVP polymer, PVP polymer, acrylate copolymer or its mixture.

27. the tablet of claim 26, wherein the fats and grease separation are from cocoa butter, butter, lard, polyethers ethylene glycol esters.

28. the tablet of claim 26, wherein the higher fatty acids is selected from stearic acid, myristic acid, palmitic acid.

29. the tablet of claim 26, wherein the higher alcohol is selected from cetanol, octadecanol.

30. the tablet of claim 26, wherein the low melt wax is selected from glycerin monostearate, glyceryl monooleate, hydrogenated fat, myristyl alcohol, octadecanol, substitution and/or unsubstituted monoglyceride class, substitution and/or unsubstituted di-glycerides, substitution and/or unsubstituted triglyceride, cera flava, cera alba, Brazil wax, castor wax, Japan tallow, acetylated monoglycerides class.

31. the tablet of claim 21, wherein described oily or oily-sample material is with 400-35, the polyethylene glycol of 000 scope mean molecule quantity, polyethylene glycol 1,000, polyethylene glycol 2,000, polyethylene glycol 3,000th, polyethylene glycol 4,000, polyethylene glycol 5,000, Macrogol 6000, polyethylene glycol 7,000th, polyethylene glycol 8,000, polyethylene glycol 9,000, polyethylene glycol 10,000th, polyethylene glycol 15,000th, polyethylene glycol 20,000 or polyethylene glycol 35,000.

32. the tablet of claim 21, wherein described oily or oily-sample material is the PEO with following molecular weight：2,000-7,000,000.

33. the tablet of claim 21, wherein described oily or oily-sample material is other block copolymers of poloxamer or oxirane and expoxy propane.

34. the tablet of claim 33, wherein described poloxamer is selected from PLURONICS F87, poloxamer 237, Pluronic/Lutrol F 108 and poloxamer188.

35. the tablet of claim 33, wherein other block copolymers of the oxirane and expoxy propane come from

And/or

Series.

36. the tablet of claim 21, wherein described oily or oily-sample material is sorbitan ester.

37. the tablet of claim 36, wherein described sorbitan ester is selected from sorbitan diisopstearate, sorbitan dioleate, sorbitan monolaurate, sorbitan list isostearate, dehydrated sorbitol mono-fatty acid ester, span 40, sorbitan monostearate, sorbitan sesquialter isostearate, NOFABLE SO-992, sorbitan sesquistearate, the isostearate of sorbitan three, sorbitan trioleate and sorbitan tristearate and its mixture.

38. the tablet of claim 21, wherein described oily or oily-sample material is the mixture of different oily or oily-sample materials.

39. the tablet of claim 38, wherein the mixture is the mixture of hydrophily and/or lyophobic dust.

40. the tablet of claim 38, wherein described oily or oily-sample material is solvent or semi-solid excipient class, it is selected from polyglycolised glycerides；From the compound fat material of plant；Plant oil；Hydrogenated vegetable oil；From the natural fatty substances of animal；Aliphatic alcohols；Esters；The semi-synthetic glyceride type of liquid ester exchange；Acid amides or fatty acid alcohol amide-type, the acetate esters of single and two-glyceride, the citric acid ester type of single and two-glyceride, the lactic acid ester of single and two-glyceride, single and two-glyceride type, the polyglycereol esters of aliphatic acid, polyglycerol polyricinoleate, the propane diols esters of aliphatic acid, sorbitan monostearate, sorbitan tristearate, stearoyl dilactic acid sodium, stearoyl dilactic acid calcium, the diacetyl tartaric acid ester class of single and two-glyceride.

41. the tablet of claim 40, wherein described solvent or semi-solid excipient class are selected from propane diols.

42. the tablet of claim 40, wherein described polyglycolised glycerides are selected from Gelucire 44/14

43. the tablet of claim 40, wherein the described compound fat material from plant is selected from cupu oil and Brazil wax.

44. the tablet of claim 40, wherein the vegetable oil is selected from apricot kernel oil, coconut oil, corn oil, cotton seed oil, sesame oil, soybean oil, olive oil, castor oil, palm-kernel oil, peanut oil, rape oil, grape seed oil.

45. the tablet of claim 40, wherein the hydrogenated vegetable oil is selected from hydrogenated groundnut, hydrogenated palm kernel oil, hydrogenated cottonseed oil, oil with hydrogenated soybean, rilanit special, hydrogenated coconut oil.

46. the tablet of claim 40, wherein the natural fatty substances from animal are selected from beeswax and lanolin.

47. the tablet of claim 40, wherein the fatty alcohol is selected from cetanol, octadecanol, laruyl alcohol, myristyl alcohol, palmityl alcohol, stearic acid aliphatic alcohols.

48. the tablet of claim 40, wherein the ester is selected from tristerin, glycol stearate, ethyl oleate, isopropyl myristate.

49. the tablet of claim 40, wherein it is Miglycol 810/812 that the liquid ester, which exchanges semi-synthetic glyceride,.

50. the tablet of claim 40, wherein the acid amides or fatty alkanol amide are selected from stearmide ethanol, the diglycollic amide of fatty coconut acid.

51. the tablet described in any one of claim 15,18 or 21~50, wherein pharmaceutically acceptable liquid preparation is dispersion, it is emulsion；Micro emulsion；Or suspension.

52. the tablet described in any one of claim 45, wherein micro emulsion are from-microemulsified delivery system.

53. the tablet described in any one of claim 15,18 or 21~50, wherein the concentration of acceptable liquid preparation is 5%w/w or more than 5%w/w on the tablet Chinese traditional medicine.

54. the tablet described in any one of claim 15,18 or 21~53, further comprising one or more treatment, prevention and/or diagnosis active material.

55. the tablet of claim 54, wherein described active material is dispersed in described pharmaceutically acceptable liquid preparation.

56. the tablet of claim 54, wherein described active material is at least partially soluble in described pharmaceutically acceptable liquid preparation.

57. the tablet of claim 54, wherein described active material at least partly exists with amorphous form.

58. the tablet described in any one or 55~56 any one of claim 15,18 or 21~50, it has at least 25N hardness.

59. the tablet described in any one or 55~56 any one of claim 15,18 or 21~50, it is the tablet form with most 5% friability.

60. the tablet described in any one or 55~56 any one of claim 15,18 or 21~50, it is tested with the disintegration time of at most 15 minutes according to Ph.Eur..

61. the tablet of claim 54, wherein in the dissolving-out method test according to USP, at least 75% treatment, prevention and/or diagnosis active material was discharged in 30 minutes.

62. preparing the method for tablet, it comprises the following steps：

I) tablet for being suitable to carrying as any one of claim 1-13 is prepared, the tablet includes one or more treatments, prevention and/or diagnosis active material；

Ii the pharmaceutically acceptable liquid preparation loaded obtained from the step i) tablet for being suitable to carrying as any one of claim 14-54) is given, the liquid preparation includes one or more treatments, prevention and/or diagnosis active material, and the load time is to be enough the time limit with the tablet for being suitable to carrying described in described pharmaceutically acceptable liquid preparation saturation.

63. the method for claim 62, wherein optionally including the pharmaceutically acceptable liquid preparation of one or more treatments, prevention and/or diagnosis active material to the tablet loading for being suitable to carrying by spraying.

64. the method for claim 62, wherein being placed in the pharmaceutically acceptable liquid preparation for including one or more treatments, prevention and/or diagnosis active material to the tablet loading for being suitable to carrying in the excessive pharmaceutically acceptable liquid preparation comprising one or more treatments, prevention and/or diagnosis active material by will be suitable for the tablet of carrying.

65. any one of claim 62-64 method, wherein to equivalent to 1kg be suitable to the amount of the tablet of carrying for, step ii) in time limit at most 60 minutes.